Oral treatments are next Holy Grail for Korea and Covid
When swine flu hit the world in 2009, Tamiflu was there to save millions of lives. While the Covid-19 pandemic has focused attention on the development of vaccines, public health professionals believe treatments could be almost just as important, especially oral treatments.
The Korean government is trying to encourage companies to develop oral treatments with proven safety and efficacy. It has been monitoring the development process of local and overseas companies.
All the expenses needed to buy the treatment will be covered by the government, it said.
Race to Covid-19 oral treatment
With oral treatment being a possible game changer, domestic biopharmaceutical companies have entered a race to be the first to develop a drug.
A total of 11 domestic oral treatment candidates have received nods to start clinical trials, according to the Ministry of Food and Drug Safety. Of them, five were undergoing clinical trials as of Sept. 9.
On Sept. 8, GeneOne Life Science’s capsule-type treatment candidate GLS-1027 won approval to start Phase 2 clinical trials from the Ministry of Food and Drug Safety. The treatment is supposed to prevent Covid-19 patients from developing severe pneumonia and Phase 1 clinical trials showed meaning results confirming its safety and tolerability.
In late August, Shin Poong Pharmaceutical’s Pyramax received permission to start Phase 3 clinical trials. Pyramax was originally the company’s antimalarial treatment, and it has been developed as a Covid-19 treatment since last year.
Unlike global companies like MSD (known as Merck & Co. in the United States and Canada), Pfizer and Roche that have been developing antiviral treatments, domestic companies are focusing on a "drug repositioning" strategy. That means they are exploring existing drugs that have been approved for other diseases in order to develop a treatment for Covid-19. The safety of those treatments has been verified to a certain degree, and these drugs are often permitted to skip Phase 1 clinical trials and can be exported to many countries quickly when commercialized.
Daewoong Pharmaceutical is in talks with the Ministry of Food and Drug Safety to start Phase 3 clinical trials of its oral treatment candidate Coviblock based on the results of Phase 2 trials it disclosed in July. Originally developed and sold as a treatment for pancreatitis and reflux esophagitis under the name Foistar, the company changed its name to Coviblock and has been developing it as a treatment that prevents coronavirus from causing an infection after it enters the body.
The Kosdaq-listed Crystal Genomics’ candidate CG-CAM20 and Dong Wha Pharm’s candidate DW2008S are currently undergoing Phase 2 clinical trials.
“When we think of 2009 and 2010 [the swine flu pandemic], the existence of an oral treatment was able to prevent the further spread of the virus within communities even though a vaccine was not yet developed,” Lee Jong-koo, a professor at the Seoul National University College of Medicine, said during a Global Bioscience Conference held on Sept. 13. “It applies to the Covid-19 pandemic as well. If people can take an oral treatment quickly, it will be very helpful.”
Lee served as commissioner of the Korea Disease Control and Prevention Agency from 2007 through 2011, including during the swine flu pandemic.
Hurdles and struggles
It remains to be seen whether Korean bio companies can successfully conclude clinical trials and commercialize the drugs. Many domestic companies are struggling, with some already giving up.
On Aug. 27, Enzychem Lifesciences revealed the disappointing results of Phase 2 clinical trials of its Covid-19 oral treatment candidate EC-18. The most important data set in proving its efficacy was to prevent Covid-19 patients with light pneumonia developing severe pneumonia and acute respiratory distress syndrome within 14 days after taking the drug.
“The trials were conducted on too few patients and there were so many limitations in the clinical trial process it had to be stopped immediately when patients showed abnormal reactions,” said Enzychem Lifesciences in a statement. “Thus we were not able to properly test the drug’s efficacy.”
In late July, Daewoong shared dissatisfying results from Coviblock’s Phase 2 clinical trials. The trials were conducted on a total of 327 patients with light symptoms and aimed to see how long it took to improve the symptoms.
According to the results, patients who took Coviblock took seven days to see an improvement in symptoms while it took eight days for patients who took the placebo — which was not statistically significant.
Shin Poong also failed to produce strong results confirming Pyramax’s efficacy in its Phase 2 clinical trials. It received permission to undergo Phase 3 clinical trials from the ministry after making a pledge that it will confirm efficacy in the last round.
Companies that failed to meet goals in trials can still apply to start the next round by changing their index of evaluation. Shin Poong increased the number of participants in Phase 3 clinical trials by 12-fold, from 113 to about 1,420, in order to prove efficacy.
Bukwang Pharm also revealed discouraging Phase 2 clinical trial results for its capsule-type treatment candidate Levovir. Its most important task to prove efficacy was to show patients testing negative for the virus after taking the drug. A total of 61 patients with moderate and serious symptoms participated — 41 with Levovir and 20 with placebo drug — and about 85.3 percent of people who took Levovir tested negative while 70.6 percent of people in the control group tested negative.
The bio company changed its plan and reset its index of evaluation to “reduction of amount of virus in the body” and reconducted the Phase 2 trials. The results of second Phase 2 clinical trials will be released by the end of the month or beginning of next month.
“On the issue of whether we will start Phase 3 clinical trials, we will have a discussion with experts considering the results of two clinical trials we have conducted on the treatment candidate," said a spokesperson for Bukwang Pharm.
Money is an issue
But even if Korea's bio firms succeed in releasing oral treatments, commercializing them is a different issue. The high price of oral treatment is something that needs to be tackled.
The Korea Disease Control and Prevention Agency said it set a 16.8-billion-won ($14.4-million) budget for purchasing Covid-19 oral treatments this year and 19.4 billion won for next year — which is enough to buy drugs that could be used by about 38,000 people.
The agency also said it has been under negotiations to preorder promising oral treatments with a few global companies including MSD, although no details have been clarified.
This means that the price of oral treatment will likely be around 952,600 won per person. Many argue that such a price is too high when efficacies have not been confirmed. MSD has been conducting Phase 3 clinical trials of its oral antiviral treatment Molnupiravir, with the goal of releasing final data within the year. It is expected to seek emergency use authorization from the U.S. Food and Drug Administration in October at the earliest.
Health authorities insist that the 900,000-won price tag is not expensive when considering other expenses such as hospital bills in the absence of oral treatments.
"If patients don’t take the oral treatment, they would have to be hospitalized or visit a community treatment center. We should think about the costs for those, as well as possible losses that would be caused when they can’t participate in economic activities due to an infection," said Bae Gyeong-taek, a senior official from the Central Disease Control Headquarters, during a radio show.
"Oral treatments would make it possible for patients to stay home and watch the progress of their condition," He added. “Things will be different then.”
BY SARAH CHEA [firstname.lastname@example.org]